IL299702A - Tigit and cd112r blockade - Google Patents

Tigit and cd112r blockade

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Publication number
IL299702A
IL299702A IL299702A IL29970223A IL299702A IL 299702 A IL299702 A IL 299702A IL 299702 A IL299702 A IL 299702A IL 29970223 A IL29970223 A IL 29970223A IL 299702 A IL299702 A IL 299702A
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amino acid
seq
sequence
acid sequence
nos
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IL299702A
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Amgen Inc
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    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Claims (48)

1
1.WHAT IS CLAIMED: 1. A CD112R antigen-binding protein comprising (a) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (b) an HC CDR2 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; and (f) an LC CDR3 amino acid sequence set forth in Table A1 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity, optionally, wherein the CD112R antigen-binding protein comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 amino acid sequences for 24F1 as set forth in Table A1.
2. The CD112R antigen-binding protein of claim 1 or 2, comprising six CDR amino acid sequences listed in a single row of Table A1 or comprising six CDR amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 13-18; (b) SEQ ID NOs: 23-28; (c) SEQ ID NOs: 33-38; (d) SEQ ID NOs: 43-48; (e) SEQ ID NOs: 53-58; (f) SEQ ID NOs: 63-68; (g) SEQ ID NOs: 73-78; (h) SEQ ID NOs: 83-88, (i) SEQ ID NOs: 93-98, (j) SEQ ID NOs: 103-108, (k) SEQ ID NOs: 233-238, (l) SEQ ID NOs: 1973-1978, (m) SEQ ID NOs: 1983-1988, (n) SEQ ID NOs: 1993-1998, and (o) SEQ ID NOs: 2003-2008, optionally, wherein the CD112R antigen-binding protein comprises the six CDR amino acid sequences of SEQ ID NOs: 33-38.
3. The CD112R antigen binding protein of any one of the preceding claims, comprising (a) a HC variable region amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of Table B1; (b) a LC variable region amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of Table B1, or (c) a combination of 1 (a) and (b), optionally, wherein the CD112R antigen-binding protein comprises the HC variable region amino acid sequence and the LC variable region amino acid sequence for 24F1 as set forth in Table B1.
4. The CD112R antigen-binding protein of claim 4, comprising a pair of HC variable region and LC variable region amino acid sequences listed in a single row of Table B1 or comprising a pair of amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 11-12; (b) SEQ ID NOs: 21-22; (c) SEQ ID NOs: 31-32; (d) SEQ ID NOs: 41-42; (e) SEQ ID NOs: 51-52; (f) SEQ ID NOs: 61-62; (g) SEQ ID NOs: 71-72; (h) SEQ ID NOs: 81-82, (i) SEQ ID NOs: 91-92, (j) SEQ ID NOs: 101-102, (k) SEQ ID NOs: 231-232, (l) SEQ ID NOs: 1971-1972, (m) SEQ ID NOs: 1981-1982, (n) SEQ ID NOs: 1991-1992, and (o) SEQ ID NOs: 2001-2002, optionally, wherein the CD112R antigen-binding protein comprises a HC variable region amino acid sequence of SEQ ID NO: 31 and a LC variable region amino acid sequence of SEQ ID NO: 32.
5. The CD112R antigen binding protein of any one of the preceding claims, comprising (a) a full-length (FL) HC amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of Table B1; (b) a FL LC amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of Table B1, or (c) a combination of (a) and (b), optionally, wherein the CD112R antigen-binding protein comprises the FL HC amino acid sequence and the FL LC amino acid sequence for 24F1 as set forth in Table B1.
6. The CD112R antigen-binding protein of claim 5, comprising a pair of full-length (FL) HC and FL LC amino acid sequences listed in a single row of Table B or comprising a pair of amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 9-10; (b) SEQ ID NOs: 19-20; (c) SEQ ID NOs: 29-30; (d) SEQ ID NOs: 39-40; (e) SEQ ID NOs: 49-50; (f) SEQ ID NOs: 59-60; (g) SEQ ID NOs: 69-70; (h) SEQ ID NOs: 79-80, (i) SEQ ID NOs: 89-90, (j) SEQ ID NOs: 99-100, (k) SEQ ID NOs: 229-230, (l) SEQ ID NOs: 1969-1970, (m) SEQ ID NOs: 1979-1980, (n) SEQ ID NOs: 1989-1990, and (o) SEQ ID NOs: 1999-2000, optionally, wherein the CD112R antigen-binding protein comprises a FL HC amino acid sequence of SEQ ID NO: 29 and a FL LC amino acid sequence of SEQ ID NO: 30. 1
7. The CD112R antigen-binding protein of any one of the preceding claims, which is an antibody.
8. The CD112R antigen-binding protein of claim 7, comprising: (a) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence of SEQ ID NO: 33 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; (b) an HC CDRamino acid sequence of SEQ ID NO: 34 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence of SEQ ID NO: 35 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence of SEQ ID NO: 36 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence of SEQ ID NO: 37 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (f) an LC CDR3 amino acid sequence of SEQ ID NO: 38 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; or (b) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence of SEQ ID NO: 63 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; (b) an HC CDRamino acid sequence of SEQ ID NO: 64 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence of SEQ ID NO: 65 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence of SEQ ID NO: 66 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence of SEQ ID NO: 67 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (f) an LC CDR3 amino acid sequence of SEQ ID NO: 68 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; or (c) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence of SEQ ID NO: 83 or a variant sequence thereof which differs by only 1-4 1 amino acids or which has at least or about 90% sequence identity; (b) an HC CDRamino acid sequence of SEQ ID NO: 84 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence of SEQ ID NO: 85 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence of SEQ ID NO: 86 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence of SEQ ID NO: 87 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (f) an LC CDR3 amino acid sequence of SEQ ID NO: 88 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; or (d) comprising (a) a HC variable region amino acid sequence of SEQ ID NO :31 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of SEQ ID NO: 31; (b) a LC variable region amino acid sequence of SEQ ID NO: 32 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of SEQ ID NO: 32, or (c) a combination of (a) and (b); or (e) comprising (a) a HC variable region amino acid sequence of SEQ ID NO: 61 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of SEQ ID NO: 61; (b) a LC variable region amino acid sequence of SEQ ID NO: 62 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of SEQ ID NO: 62, or (c) a combination of (a) and (b); or (f) comprising (a) a HC variable region amino acid sequence of SEQ ID NO: 81 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of SEQ ID NO: 81; (b) a LC variable region amino acid sequence of SEQ ID NO: 82 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable 1 region amino acid sequence of SEQ ID NO: 82, or (c) a combination of (a) and (b); or (g) (a) a full-length (FL) HC amino acid sequence of SEQ ID NO: 29 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of SEQ ID NO: 29; (b) a FL LC amino acid sequence set forth of SEQ ID NO: 30 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of SEQ ID NO: 30, or (c) a combination of (a) and (b); or (h) (a) a full-length (FL) HC amino acid sequence of SEQ ID NO: 59 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of SEQ ID NO: 59; (b) a FL LC amino acid sequence set forth of SEQ ID NO: 60 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of SEQ ID NO: 60, or (c) a combination of (a) and (b); or (i) (a) a full-length (FL) HC amino acid sequence of SEQ ID NO: 79 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of SEQ ID NO: 79; (b) a FL LC amino acid sequence set forth of SEQ ID NO: 80 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of SEQ ID NO: 80, or (c) a combination of (a) and (b).
9. The CD112R antigen-binding protein of any one of claims 1-6, which is an antigen-binding fragment of an antibody.
10. The CD112R antigen-binding protein of any one of claims 1-6, which is an antibody protein product, optionally, an scFv.
11. A nucleic acid encoding the CD112R antigen binding protein of any one of the preceding claims.
12. A nucleic acid encoding the light chain, the heavy chain, or both the light chain and the heavy chain of the antibody of claim 7 or 8. 1
13. The nucleic acid of claim 11 or 12 wherein the nucleotide sequence encodes (a) a HC variable region amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of Table B1; (b) a LC variable region amino acid sequence set forth in Table B1 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of Table B1, or (c) both (a) and (b).
14. A vector comprising one or more nucleic acids of any one of claims 11 to 13.
15. A host cell comprising one or more nucleic acids of any one of claims 11 to 13 or one or more vectors of claim 14.
16. The host cell of claim 15, wherein the host cell produces a CD112R antigen binding protein of any of claims 1-10.
17. A TIGIT antigen-binding protein comprising (a) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (b) an HC CDR2 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; and (f) an LC CDR3 amino acid sequence set forth in Table A2 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity, optionally, wherein the CD112R antigen-binding protein comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 amino acid sequences for 43B7.002.015 as set forth in Table A2.
18. The TIGIT antigen binding protein of embodiment 17, comprising: (a) a LC CDR1 amino acid sequence comprising Gln27 , or a conservative amino acid substitution thereof, Ser28 , or a conservative amino acid substitution thereof, or any 1 combination thereof; a LC CDR2 amino acid sequence comprising Glu1 , or a conservative amino acid substitution thereof; and a LC CDR3 amino acid sequence comprising Ser91,or a conservative amino acid substitution thereof, Ser92 , or a conservative amino acid substitution thereof, Ser93 , or a conservative amino acid substitution thereof, Leu94 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR1 amino acid sequence comprising Val32 , or a conservative amino acid substitution thereof, Tyr33 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR2 amino acid sequence comprising Tyr52 , or a conservative amino acid substitution thereof, Tyr54 , or a conservative amino acid substitution thereof, Tyr55 , or a conservative amino acid substitution thereof, Ser56 , or a conservative amino acid substitution thereof, Gly57 , or a conservative amino acid substitution thereof, Gly58 , or a conservative amino acid substitution thereof, Thr59 , or a conservative amino acid substitution thereof, Tyr60 , or a conservative amino acid substitution thereof, Pro63 , or a conservative amino acid substitution thereof, Arg66 , or a conservative amino acid substitution thereof, or any combination thereof; and a HC CDR3 amino acid sequence comprising Ile102 , or a conservative amino acid substitution thereof, Ala104 , or a conservative amino acid substitution thereof, Gly107 , or a conservative amino acid substitution thereof, Tyr108 , or a conservative amino acid substitution thereof, Phe109 , or a conservative amino acid substitution thereof, Tyr110 , or a conservative amino acid substitution thereof, Tyr111 , or a conservative amino acid substitution thereof, or any combination thereof; wherein the position number is relative the LC variable region amino acid sequence of the TIGIT antigen binding protein (b) a LC CDR1 amino acid sequence comprising Gln27 , or a conservative amino acid substitution thereof, Ser28 , or a conservative amino acid substitution thereof, Val29 , or a conservative amino acid substitution thereof, Ser30 , or a conservative amino acid substitution thereof, Ser31 , or a conservative amino acid substitution thereof, Thr32 , or a conservative amino acid substitution thereof, Tyr33 , or a conservative amino acid substitution thereof, or any combination thereof; a LC CDR2 amino acid sequence comprising Glu1 , or a conservative amino acid substitution thereof, Ile2 , or a conservative amino acid substitution thereof, Ser68 , or a conservative amino acid substitution thereof, Gly69 , or a conservative amino acid substitution thereof, or any combination thereof; a LC CDR3 amino acid sequence comprising Tyr92,or a conservative amino acid substitution thereof, Asp93 , or a conservative amino acid 1 substitution thereof, Val94 , or a conservative amino acid substitution thereof, Ser95 , or a conservative amino acid substitution thereof, Pro96 , or a conservative amino acid substitution thereof, Trp97 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR1 amino acid sequence comprising Gly32 , or a conservative amino acid substitution thereof, Tyr35 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR2 amino acid sequence comprising Tyr52 , or a conservative amino acid substitution thereof, Tyr54 , or a conservative amino acid substitution thereof, Tyr55 , or a conservative amino acid substitution thereof, Ser56 , or a conservative amino acid substitution thereof, Ser58 , or a conservative amino acid substitution thereof, Thr59 , or a conservative amino acid substitution thereof, Phe60 , or a conservative amino acid substitution thereof, Pro63 , or a conservative amino acid substitution thereof, Lys66 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR3 amino acid sequence comprising Arg102 , or a conservative amino acid substitution thereof, Asn104 , or a conservative amino acid substitution thereof, Trp105 , or a conservative amino acid substitution thereof, Asn106 , or a conservative amino acid substitution thereof, Tyr107 , or a conservative amino acid substitution thereof, or any combination thereof; wherein the position number is relative the LC variable region amino acid sequence of the TIGIT antigen binding protein (c) a LC CDR1 amino acid sequence comprising Arg30 , or a conservative amino acid substitution thereof, Arg31 , or a conservative amino acid substitution thereof, Tyr32 , or a conservative amino acid substitution thereof, or any combination thereof; a LC CDR3 amino acid sequence comprising Ser91,or a conservative amino acid substitution thereof, Tyr92 , or a conservative amino acid substitution thereof, Ser93 , or a conservative amino acid substitution thereof, Thr94 , or a conservative amino acid substitution thereof, or any combination thereof., wherein the position number is relative the LC variable region amino acid sequence of the TIGIT antigen binding protein; a HC CDR1 amino acid sequence comprising Thr30 , or a conservative amino acid substitution thereof, Gly31 or a conservative amino acid substitution thereof, Tyr32 , or a conservative amino acid substitution thereof, Tyr33 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR2 amino acid sequence comprising Trp47 , or a conservative amino acid substitution thereof, a Trp50 , or a conservative amino acid substitution thereof, Ser52 , or a conservative amino acid substitution thereof, Thr54 , or a conservative 1 amino acid substitution thereof, Ser55 , or a conservative amino acid substitution thereof, Ala57 , or a conservative amino acid substitution thereof, Thr58 , or a conservative amino acid substitution thereof, Gly59 , or a conservative amino acid substitution thereof, Tyr60 , or a conservative amino acid substitution thereof, Gln65 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR3 amino acid sequence comprising Asn101 , or a conservative amino acid substitution thereof, Ser102 , or a conservative amino acid substitution thereof, Val103 , or a conservative amino acid substitution thereof, Leu104 , or a conservative amino acid substitution thereof, Tyr105 , or a conservative amino acid substitution thereof, Tyr106 , or a conservative amino acid substitution thereof, Tyr107 , or a conservative amino acid substitution thereof, or any combination thereof; wherein the position number is relative the HC variable region amino acid sequence of the TIGIT antigen binding protein; (d) a LC CDR1 amino acid sequence comprising Gln27 , or a conservative amino acid substitution thereof, Leu30 , or a conservative amino acid substitution thereof, Ser32 , or a conservative amino acid substitution thereof, or any combination thereof; a LC CDR3 amino acid sequence comprising Ser96,or a conservative amino acid substitution thereof, Ile97 , or a conservative amino acid substitution thereof, Gln98 , or a conservative amino acid substitution thereof, Leu99 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR1 amino acid sequence comprising Asp33 , or a conservative amino acid substitution thereof; a HC CDR2 amino acid sequence comprising Tyr52 , or a conservative amino acid substitution thereof, a Tyr54 , or a conservative amino acid substitution thereof, Tyr55 , or a conservative amino acid substitution thereof, Ser56 , or a conservative amino acid substitution thereof, Gly57 , or a conservative amino acid substitution thereof, Gly58 , or a conservative amino acid substitution thereof, Thr59 , or a conservative amino acid substitution thereof, Tyr60 , or a conservative amino acid substitution thereof, Pro63 , or a conservative amino acid substitution thereof, Lys66 , or a conservative amino acid substitution thereof, or any combination thereof; a HC CDR3 amino acid sequence comprising Ile102 , or a conservative amino acid substitution thereof, Ala104 , or a conservative amino acid substitution thereof, Gly107 , or a conservative amino acid substitution thereof, Tyr108 , or a conservative amino acid substitution thereof, Phe109 , or a conservative amino acid substitution thereof, Tyr110 , or a conservative amino acid substitution thereof, Phe111 , or a 1 conservative amino acid substitution thereof, or any combination thereof; wherein the position number is relative the HC variable region amino acid sequence of the TIGIT antigen binding protein.
19. The TIGIT antigen-binding protein of claim 17 or 18, comprising six CDR amino acid sequences listed in a single row of Table A2 or comprising six CDR amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 113-118; (b) SEQ ID NOs: 123-128; (c) SEQ ID NOs: 133-138; (d) SEQ ID NOs: 143-148; (e) SEQ ID NOs: 153-158; (f) SEQ ID NOs: 163-168; (g) SEQ ID NOs: 173-178; (h) SEQ ID NOs: 183-188, (i) SEQ ID NOs: 193-198, (j) SEQ ID NOs: 203-208, (k) SEQ ID NOs: 213-218, (l) SEQ ID NOs: 223-228, and (m) SEQ ID NOs: 2013-2018, optionally, wherein the TIGIT antigen-binding protein comprises the six CDR amino acid sequences of SEQ ID NOs: 203-208.
20. The TIGIT antigen binding protein of any one of claims 17-19, comprising (a) a HC variable region amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of Table B2; (b) a LC variable region amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of Table B2, or (c) a combination of (a) and (b), optionally, wherein the TIGIT antigen-binding protein comprises the HC variable region amino acid sequence and the LC variable region amino acid sequence for 43B7.002.015 as set forth in Table B2.
21. The TIGIT antigen-binding protein of claim 20, comprising a pair of HC variable region and LC variable region amino acid sequences listed in a single row of Table B2 or comprising a pair of amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 111-112, (b) SEQ ID NOs: 121-122, (c) SEQ ID NOs: 131-132, (d) SEQ ID NOs: 141-142, (e) SEQ ID NOs: 151-152, (f) SEQ ID NOs: 161-162, (g) SEQ ID NOs: 171-172, (h) SEQ ID NOs: 181-182, (i) SEQ ID NOs: 191-192, (j) SEQ ID NOs: 201-202, (k) SEQ ID NOs: 211-212, (l) SEQ ID NOs: 221-222, and (m) SEQ ID NOs: 2011-2012, optionally, wherein the TIGIT antigen-binding protein comprises a HC variable region amino acid sequence of SEQ ID NO: 201 and LC variable region amino acid sequence of SEQ ID NO: 202. 1
22. The TIGIT antigen binding protein of any one of claims 17-21, comprising (a) a full-length (FL) HC amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of Table B2; (b) a FL LC amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of Table B2, or (c) a combination of (a) and (b), optionally, wherein the TIGIT antigen-binding protein comprises the FL HC amino acid sequence and the FL LC amino acid sequence for 43B7.002.015 as set forth in Table B2.
23. The TIGIT antigen-binding protein of claim 22, comprising a pair of full-length (FL) HC and FL LC amino acid sequences listed in a single row of Table B2 or comprising a pair of amino acid sequences selected from the group consisting of: (a) SEQ ID NOs: 109-110, (b) SEQ ID NOs: 119-120, (c) SEQ ID NOs: 129-130, (d) SEQ ID NOs: 139-140, (e) SEQ ID NOs: 149-150, (f) SEQ ID NOs: 159-160, (g) SEQ ID NOs: 169-170, (h) SEQ ID NOs: 179-180, (i) SEQ ID NOs: 189-190, (j) SEQ ID NOs: 199-200, (k) SEQ ID NOs: 209-210, (l) SEQ ID NOs: 219-220, and (m) SEQ ID NOs: 2009-2010, optionally, wherein the TIGIT antigen-binding protein comprises a FL HC amino acid sequence of SEQ ID NO: 199 and FL LC amino acid sequence of SEQ ID NO: 200.
24. The TIGIT antigen-binding protein of any one of claims 17-23, which is an antibody.
25. The TIGIT antigen-binding protein of claim 24, comprising: (a) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence of SEQ ID NO: 203 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; (b) an HC CDRamino acid sequence of SEQ ID NO: 204 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence of SEQ ID NO: 205 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence of SEQ ID NO: 206 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence of SEQ ID NO: 207 or a variant sequence thereof which differs by only 1-4 amino acids or 1 which has at least or about 90% sequence identity; (f) an LC CDR3 amino acid sequence of SEQ ID NO: 208 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; or (b) a heavy chain (HC) complementarity-determining region (CDR) 1 amino acid sequence of SEQ ID NO: 223 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; (b) an HC CDRamino acid sequence of SEQ ID NO: 224 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (c) an HC CDR3 amino acid sequence of SEQ ID NO: 225 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (d) a light chain (LC) CDR1 amino acid sequence of SEQ ID NO: 226 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (e) an LC CDR2 amino acid sequence of SEQ ID NO: 227 or a variant sequence thereof which differs by only 1-4 amino acids or which has at least or about 90% sequence identity; (f) an LC CDR3 amino acid sequence of SEQ ID NO: 228 or a variant sequence thereof which differs by only 1-amino acids or which has at least or about 90% sequence identity; or (c) comprising (a) a HC variable region amino acid sequence of SEQ ID NO :201 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of SEQ ID NO: 201; (b) a LC variable region amino acid sequence of SEQ ID NO: 202 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of SEQ ID NO: 202, or (c) a combination of (a) and (b); or (d) comprising (a) a HC variable region amino acid sequence of SEQ ID NO: 221 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of SEQ ID NO: 221; (b) a LC variable region amino acid sequence of SEQ ID NO: 222 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of SEQ ID NO: 222, or (c) a combination of (a) and (b); or 1 (e) (a) a full-length (FL) HC amino acid sequence of SEQ ID NO: 199 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of SEQ ID NO: 199; (b) a FL LC amino acid sequence set forth of SEQ ID NO: 200 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of SEQ ID NO: 200, or (c) a combination of (a) and (b); or (f) (a) a full-length (FL) HC amino acid sequence of SEQ ID NO: 219 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL HC amino acid sequence of SEQ ID NO: 219; (b) a FL LC amino acid sequence set forth of SEQ ID NO: 220 or a variant sequence thereof which differs by only 1-50 amino acids or which has at least or about 90% or about 95% sequence identity to the FL LC amino acid sequence of SEQ ID NO: 220, or (c) a combination of (a) and (b).
26. The TIGIT antigen-binding protein of any one of claims 17-23, which is an antigen-binding fragment of an antibody.
27. The TIGIT antigen-binding protein of any one of claims 17-23, which is an antibody protein product, optionally, an scFv.
28. A nucleic acid encoding the TIGIT antigen binding protein of any one of the preceding claims.
29. A nucleic acid encoding the light chain, the heavy chain or both the light chain and the heavy chain of the antibody of claim 24 or 25.
30. The nucleic acid of claim 28 or 29, wherein the nucleotide sequence encodes (a) a HC variable region amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the HC variable region amino acid sequence of Table B2; (b) a LC variable region amino acid sequence set forth in Table B2 or a variant sequence thereof which differs by only 1-15 amino acids or which has at least or about 90% or about 95% sequence identity to the LC variable region amino acid sequence of Table B2, or (c) both (a) and (b).
31. A vector comprising one or more nucleic acids of any one of claims 28 to 30. 1
32. A host cell comprising one or more nucleic acids of any one of claims 28 to 30 or one or more vectors of claim 31.
33. The host cell of claim 31, wherein the host cell produces a TIGIT antigen binding protein of any of claims 17-27.
34. A composition comprising a CD112R antigen binding protein of any one of claims 1-10 and a TIGIT antigen binding protein of any one of claims 17-27, optionally, wherein the composition comprises a CD112R antigen-binding protein comprising a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NOs: 33-38, respectively, and a TIGIT antigen-binding protein comprising a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NOs: 203-208, respectively.
35. The composition of claim 34, wherein (A) the CD112R antigen binding protein is 1E1, 1E1.016, 24F1, 29E10, 24F1.001, 29E10_CONS.020, 29E10_CONS.021, 29E10_CONS.022, 29E10_CONS.025, 11E4, 31B3, 27G12, 28F9, 28H7, or 36C8 as described in Table A1 or Table B1, optionally, 24F1, 29E10_CONS.020 or 29E10_CONS.022, (B) the TIGIT antigen binding protein is any one of 55G7.041.008, 58A7.003.008.075, 4G10, 11A3, 28B8, 39D2, 43B7, 55G7, 66H9, 43B7.002.015, 58A7.003.08, 66H9.009, or 58A7 as described in Table A2 or Table B2, optionally, the 43B7.002.015 or 66H9.009, or a combination of (A) and (B).
36. The composition of claim 34 or 35, wherein the composition comprises (A) 24F1 and 43B7.002.015, (B) 24F1 and 66H9.009, (C) 29E10_CONS.020 and 43B7.002.015, (D) 29E10_CONS.020 and 66H9.009, (E) 29E10_CONS.022 and 43B7.002.015, (F) 29E10_CONS.022 and 66H9.009, (G) 43B7.002.015 and 1E1.016, (H) 43B7.002.015 and 24F1, (I) 43B7.002.015 and 29E10, (J) 66H9.009 and 1E1.016, (K) 66H9.009 and 29E10, (L) 43B7 and 29E10, (M) 43B7 and 24F1, or (N) 43B7 and 11E4.
37. The composition of any one of claims 34-36, wherein the CD112R antigen binding protein and the TIGIT antigen binding protein is present in the composition at a ratio of about 1:1.
38. The composition of any one of claims 34-37 further comprising a PD-1 antigen binding protein.
39. A kit comprising an antigen-binding protein of any one of claims 1-10 and 17-27, the nucleic acid of any one of claims 11-13 and 28-30, the vector of claim 14 or 31, the host cell of any 1 one of claims 15, 16, 32, and 33, a composition of any one of claims 34-38, or a combination thereof, and a container.
40. The kit of claim 39 further comprising a PD-1 antigen binding protein.
41. A pharmaceutical composition comprising an antigen-binding protein of any one of claims 1-and 17-27, the nucleic acid of any one of claims 11-13 and 28-30, the vector of claim or 31, the host cell of any one of claims 15, 16, 32, and 33, a composition of any one of claims 33-36, or a combination thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.
42. The pharmaceutical composition of claim 41 further comprising a PD-1 antigen binding protein.
43. A method of making CD112R antigen-binding protein comprising culturing the host cell of any one of claims 15 or 16 so as to express the CD112R antigen-binding protein and harvesting the expressed CD112R antigen-binding protein.
44. A method of making TIGIT antigen-binding protein comprising culturing the host cell of any one of claims 32 or 33 so as to express the TIGIT antigen-binding protein and harvesting the expressed TIGIT antigen-binding protein.
45. A method of treating a subject in need thereof, comprising administering to the subject in need thereof a pharmaceutical composition of claim 41 or 42 in an amount effective to treat the subject.
46. The method of claim 45, wherein the subject has a solid tumor and the pharmaceutical composition is administered to the subject in an amount effective to treat the solid tumor in the subject.
47. A method of treating a subject in need thereof, comprising administering to the subject in need thereof a first pharmaceutical composition comprising a CD112R antigen-binding protein and a TIGIT antigen-binding protein and a second pharmaceutical composition comprising a PD-1 inhibitor. 1
48. The method of claim 47, wherein the subject has a solid tumor and the first pharmaceutical composition and the second pharmaceutical composition are administered to the subject in amounts effective to treat the solid tumor in the subject.
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